Protein Biomarkers for the Early Detection of Breast Cancer

Abstract

Advances in breast cancer control will be greatly aided by early detection so as to diagnose and treat breast cancer in its preinvasive state prior to metastasis. For breast cancer, the second leading cause of cancer-related death among women in the United States, early detection does allow for increased treatment options, including surgical resection, with a corresponding better patient response. Unfortunately, however, many patients' tumors are diagnosed following metastasis, thus making it more difficult to successfully treat the malignancy. There are, at present, no existing validated plasma/serum biomarkers for breast cancer. Only a few biomarkers (such as HER-2/neu, estrogen receptor, and progesterone receptor) have utility for diagnosis and prognosis. Thus, there is a great need for new biomarkers for breast cancer. This paper will focus on the identification of new serum protein biomarkers with utility for the early detection of breast cancer.

Alpha 2HS-glycoprotein, a tumor-associated antigen (TAA) detected in Mexican patients with early-stage breast cancer

“…However, the mechanisms leading to autoantibody production in patients with cancer are not completely understood; emerging evidence indicates that the majority of tumorassociated antigens (TAA) are cellular proteins whose aberrant regulation of function could be linked with malignancy [37][38][39]. Tumor-associated antigens can emerge through different mechanisms, such as encoding DNA mutations that lead to new epitopes in expressed proteins (e.g., p53), posttranslational modifications with immunological relevance [e.g., under-glycosylated MUC1] [45], and altered tissue-specific expression patterns or levels that can lead to the exposure of antigens usually expressed solely in immunoprivileged sites [e.g., NY-ESO-1] [46].…”

Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer

“…Because it is known that certain proteases/peptidases play an important role in several cancers, a deeper understanding of certain proteolytic events, particularly in the tumor microenvironment, will facilitate the identification of tumor-derived products that are eventually secreted into circulation (8, 12, 33, 34). Profiling the serum proteome then provides a “map” that we can use to trace cancer-specific metabolic or immunological signatures indicative of early-stage tumor progression (6, 13, 35, 36). …”

“…In theory, any or all of these secreted proteins can serve as the biomarkers of tumor progression (3, 4). However, the reality is much more challenging to monitor because of the large degree of fluctuation in abundance and localization of these tumor-secreted proteins, especially in the early stage of tumor development and/or metastasis (5, 6). As such, it seems feasible that we might take advantage of the fact that secreted proteases/peptidases in the tumor microenvironment generate proteolytic products, also referred to as “circulating peptides”, and these are continuously released into interstitial fluid, lymph, eventually making their way into the bloodstream (7).…”

Comparative study of Her-2, p53, Ki-67 expression and clinicopathological characteristics of breast cancer in a cohort of northern China female patients

“…These receptors are single transmembrane proteins consisting of an intracellular tyrosine binding domain with various tyrosine phosphorylation sites 5,6 and an extracellular domain for ligand binding and a cytoplasmic tail. 7 After dimerization, Her-2 induces various cellular functions such as cell growth, differentiation and survival through a different cascade. Through MAPK and PI3K signaling pathways, Her-2 prevents apoptosis and promotes cell proliferation.…”